A 16-week, multicenter, randomized, double blind, parallel-group study was performed to examine whether additional administration of mitiglinide improves glycemic control in Japanese type 2 diabetic patients who are insufficiently controlled by pioglitazone monotherapy. Japanese adult type 2 diabetic patients were at first treated with diet plus pioglitazone 15−30 mg/day for 4 weeks then randomized to receive additional mitiglinide 5 or 10 mg or placebo tid for a further 16 weeks. In all, 381 patients were randomized. At final evaluation, glycated hemoglobin (HbA_1C) was reduced by (mean ± SD) −0.02 ± 0.60% in the pioglitazone monotherapy group and by −0.45 ± 0.77% and −0.67 ± 0.59% in the mitiglinide 5 and 10 mg combination groups, respectively (both p<0.001 vs. pioglitazone monotherapy group). The percentage of patients who achieved HbA_1C targets was significantly (p<0.001) higher in the mitiglinide combination groups than in the pioglitazone monotherapy group. Significant improvements in fasting plasma glucose and postprandial plasma glucose were noted in the mitiglinide combination groups versus the pioglitazone monotherapy group. No increase in adverse events was noted when mitiglinide was administered concomitantly with pioglitazone monotherapy. Hypoglycemic adverse events were infrequently and similarly observed in all three groups. Body weight gain and edema presented no clinical problem. HbA_1C was significantly improved in the mitiglinide combination groups compared with the pioglitazone monotherapy group, and significantly more patients achieved HbA_1C targets. Therefore mitiglinide effectively improves glycemic control in type 2 diabetic patients who are inadequately controlled by pioglitazone monotherapy.